O-Xylene → N-(1-cyclohexylmethylpiperid-4-yl)-2-methoxy-4-acetamido-5-chlorobenzamide

HRID 261054Notes

Reaction equation

HRID 261054 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([NH:13][C:14](=[O:16])[CH3:15])[C:10]([Cl:17])=[CH:9][C:4]=1[C:5]([O:7]C)=O.C1(C)C(C)=CC=CC=1.[CH:26]1([CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-]>CO>[CH:26]1([CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([NH:39][C:5](=[O:7])[C:4]3[CH:9]=[C:10]([Cl:17])[C:11]([NH:13][C:14](=[O:16])[CH3:15])=[CH:12][C:3]=3[O:2][CH3:1])[CH2:35][CH2:34]2)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1

Participants

6

Reactant 4

HCID 7237O-XyleneHCID 11143Aluminum isopropoxideHCID 77721Methyl 4-acetamido-5-chloro-2-methoxybenzoateHCID 64969411-(Cyclohexylmethyl)piperidin-4-amine

Product 1

HCID 20395820N-(1-cyclohexylmethylpiperid-4-yl)-2-methoxy-4-acetamido-5-chlorobenzamideYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 2-methoxy-4-acetamido-5-chlorobenzoate (25.7 g; 0.1 moles), xylene (80 ml), 1-cyclohexylmethyl-4-aminopiperidine (21.6 g; 0.11 moles) and aluminium isopropoxide (5 g) was heated to the boiling point whilst methanol was distilled off as it was formed. When the theoretical quantity of methanol was removed, the xylene was distilled off and the residue was dissolved in 2 N hydrochloric acid (200 ml). The aqueous solution was made alkaline with sodium hydroxide solution, extracted with chloroform and the chloroformic layer evaporated to dryness to give N-(1-cyclohexylmethylpiperid-4-yl)-2-methoxy-4-acetamido-5-chlorobenzamide (27 g). Its hydrochloride monohydrate was prepared by the procedure described in Example 2, m.p. 219°-221° C.

Workup

  1. distillationwas distilled off as it
  2. customwas formed
  3. customWhen the theoretical quantity of methanol was removed
  4. distillationthe xylene was distilled off
  5. dissolutionthe residue was dissolved in 2 N hydrochloric acid (200 ml)
  6. extractionextracted with chloroform
  7. customthe chloroformic layer evaporated to dryness

Sources & evidence

ORD record
ord-6526178ff28f401ab462433339e6bcaf
Source dataset
uspto-grants-1979_08
Patent number
US04163789

Reaction notes

Loading…